Voprosy virusologii · 2025
Modeling of mixed infection with Zika and West Nile viruses (Flaviviridae: Orthoflavivirus: Orthoflavivirus zikaense, Orthoflavivirus nilense) in vitro and in vivo.
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Svyatchenko V A, Protopopova E V, Legostaev S S, Mikryukova T P, Agafonov A P, Loktev V B
Аннотация
INTRODUCTION: Mosquito-borne human diseases caused by Zika virus and West Nile virus (WNV) are widespread across multiple continents and cause major outbreaks. Their ranges overlap and the possibility of mixed infections is obvious. The information of such mixed infections is limited. The aim of the study is to investigate the features of mixed infection of WNV and Zika virus in vitro and in vivo in order to assess their possible interference and/or enhancement of viral infection.
MATERIALS AND METHODS: The study used West Nile virus and Zika virus strains Vlg27924 and MR766, respectively. The infectious activity of viruses during mono- and co-infection was determined on Vero E6 cell culture using RT-PCR, as well as on BALB/c mice using various administration schemes.
RESULTS: In vitro studies of co-infection with WNV and Zika virus showed that co-infection leads to interference, with the degree of competitive inhibition of replication being more pronounced for Zika virus, reaching 1000 times or more when compared to mono-infection. During simultaneous infection in mice, Zika virus does not affect the development of lethal infection caused by WNV. However, preliminary (4 and 20 days) infection with a sublethal dose of Zika virus reliably protects animals from subsequent administration of 10 and 100 LD50 WNV, respectively. In pre-infected and co-infected animals with Zika virus, the development of WNV-specific viral neutralizing antibodies was recorded in higher titers than in WNV monoinfected animals.
CONCLUSION: The presence of in vitro interference between the studied orthoflaviviruses was shown, most pronounced in relation to the Zika virus. No significant effect was observed with simultaneous co-infection in vivo. However, pre-infection of mice with Zika virus provides protection to animals from lethal WNV infection due to the induction of high levels of antibodies that specifically neutralize its infectious activity.
MATERIALS AND METHODS: The study used West Nile virus and Zika virus strains Vlg27924 and MR766, respectively. The infectious activity of viruses during mono- and co-infection was determined on Vero E6 cell culture using RT-PCR, as well as on BALB/c mice using various administration schemes.
RESULTS: In vitro studies of co-infection with WNV and Zika virus showed that co-infection leads to interference, with the degree of competitive inhibition of replication being more pronounced for Zika virus, reaching 1000 times or more when compared to mono-infection. During simultaneous infection in mice, Zika virus does not affect the development of lethal infection caused by WNV. However, preliminary (4 and 20 days) infection with a sublethal dose of Zika virus reliably protects animals from subsequent administration of 10 and 100 LD50 WNV, respectively. In pre-infected and co-infected animals with Zika virus, the development of WNV-specific viral neutralizing antibodies was recorded in higher titers than in WNV monoinfected animals.
CONCLUSION: The presence of in vitro interference between the studied orthoflaviviruses was shown, most pronounced in relation to the Zika virus. No significant effect was observed with simultaneous co-infection in vivo. However, pre-infection of mice with Zika virus provides protection to animals from lethal WNV infection due to the induction of high levels of antibodies that specifically neutralize its infectious activity.